Small nuclear ribonucleoproteins (snRNPs) are complexes with both RNA and protein components located in the nucleus of all eukaryotic cells. They are involved in various cell processes including mRNA splicing, tRNA processing, and rRNA maturation. At least 5 snRNPs have been identified, each with a specific RNA and one or more specific protein components. In addition, there are a group of eight common proteins that bind tightly to, and are shared by all snRNPs. These molecules, known as the Sm proteins, were originally identified as targets of auto-antibodies from systemic lupus erythematosus (SLE) patients (Lerner MR et al (1979) Proc Natl Acad Sci 76:5495-5499).
Raker VA et al (1996, EMBO J 15: 2256-2269) have shown that Sm proteins are necessary for snRNP biogenesis. Cross-reactivity of Sm proteins suggests that they share common epitopes. Sequence information, in a broad range of Sm proteins from several species, revealed conserved amino acid residues and hydrophobicity within two shared motifs (Seraphin B (1995) EMBO J 14: 2089-2098; Hermann H et al (1995) EMBO J 14: 2076-2088). Sequencing information generated by large-scale sequencing projects in Caenorhabditis elegans and Saccharomyces cerevisiae have revealed additional Sm homologs (Wilson R et al (1994) Nature 368: 32-38; Mallet L et al, unpublished; Van Dyck L et al (1994) Yeast 10: 1663-1673).
Sm Proteins and Disease
SLE is a systemic autoimmune disorder producing a chronic inflammatory disease affecting all organ systems. SLE is unpredictable and often fatal, with renal involvement being the most prevalent life threatening complication. Tests for extractable nuclear antigens, and in particular Sm proteins, are diagnostic for SLE. Anti-Sm antibodies are highly specific to SLE and may also have an important role in the pathogenesis of the disease (Tomer Y et al (1993) Int Arch Allergy Immunol 100: 293-306).
Molecules that are antigenically related to the myelin basic protein are being used in the treatment of multiple sclerosis, another autoimmune disorder (Grgacic E et al (1990) Int Immunol 2: 713-718). It is believed that the immune response can be suppressed by protein fragments which are antigenically related to the target of immune system attack (Teitelbaum D et al (1996) J Neuroimmunol 64: 209-217).
The discovery of additional snRNP Sm genes may provide agents which are more effective in SLE diagnosis and treatment than known agents. A new snRNP Sm protein would satisfy a significant need in the art by providing new agents for the diagnosis, prevention, and treatment of SLE.